4. Normative standards

The formulation of basal metabolic standards has resulted in the
development of an extensive literature; work pertinent to infants will be
reviewed (BENEDICT and TALBOT, 1921; LEVINE and MARPLES, 1931; KARLBERG, 1952;
LEE and ILIFF, 1956; SCHOFIELD, 1985).

Extensive observations on the basal metabolism of 77 normal
infants (40 boys and 33 girls, ages 8 days to 25 months) were used to derive
normal standards (BENEDICT and TALBOT, 1921). Observations of basal metabolism
were made during sleep with minimal extraneous muscular activity and minimal
influence of food (1 to 1.5 hour after the ingestion of a small meal). Total
basal expenditure increased with body weight; the low expenditure (kcal/kg/d)
after birth increased to a maximum at approximately 1 to 2 years, with a
tendency to decrease thereafter. The values of 23 individuals studied
longitudinally, however, did not consistently show the trend of the composite
curves. A number of physiological factors were found to influence basal
metabolism, such as weight, length, and age, although weight had by far the
greatest influence. By means of partial correlation, independent effects of
weight, height, and age on metabolism were establish ed. Benedict noted a
profound physiological difference in the metabolism of infants who weighed 6 to
8 kg; this greater metabolic intensity per unit active protoplasmic tissue,
however, was not substantiated by other investigators.

LEVINE and MARPLES (1931) revised prediction curves for basal
metabolism based on the data of BENEDICT and TALBOT (1921). The standards were
derived from 137 observations of infants, aged 8 days to 25 months. Benedict
claimed that these infants were normal and typical of infants at large; by
Levine's assessment the infants were underweight for age. High correlations
were detected between basal metabolism and age (r = 0.91), weight (r = 0.95),
length (r = 0.96), and body surface area (r = 0.96). Independent effects of age,
weight, height, and body surface on heat production were demonstrated, but the
influence of age was apparently trivial. A multiple regression equation using
weight and height was derived from the data:

c = 28.12 WT +8.40 HT -362.18

where calories (c) are expressed in kcal/24 h, weight (WT) in kg,
and height (HT) in cm.

In Scandinavia, KARLBERG (1952) performed extensive studies on 60
normal infants who ranged in age from 1 week to 1 year. Karlberg's
measurements were made on fasted infants in the morning or early forenoon; a
barbituric acid (Hexobarbital) preparation was used as a sedative. Among infants
of the same weight, thin infants had higher metabolic rates than normal weight
and overweight infants. Among infants of the same height, thin infants had lower
expenditures than average-sized infants. Karlberg's standards were based on
weight and height for infants 1 week to 1 year of age:

c = WT.611 * HT.951 * 0.0829

where calories (c) are expressed in kcal/h, weight (WT) in kg, and
height (HT) in cm.

LEE and ILIFF (1956) measured the basal metabolism of 78 healthy
infants (aged 1 through 37 months) in an open-circuit chamber within 3.5 hours
of feeding. No significant trend in energy expenditure, standardized by body
weight, was demonstrated with age. There was substantial individual variation in
energy expenditure over time; many of the individual curves peaked somewhere
between 5 to 16 months.

Schofield compiled data of basal metabolism from BENEDICT and
TALBOT (1914, 1921), CLAGETT and HATHAWAY (1941), HARRIS and BENEDICT (1919),
and KARLBERG (1952). Predictive models were developed and the relative
contributions to basal metabolism of various independent variables i.e., age,
sex, weight, height, and weight/height were assessed. As expected, there were
strong relationships between all measures; height and weight predicted BMR, as
did the more complicated variables. For the under-3-years age group, height
contributed significantly to the prediction of BMR. The following equations were
computed with which to predict the BMR of children under 3 years:

m BMR = 0.249 WT - 0.127

R = 0.95 SEE = 0.292

f BMR = 0.244 WT - 0.130

R = 0.96 SEE = 0.245

m BMR = 0.0007 WT + 6.349 HT - 2.584

R = 0.97 SEE = 0.242

f BMR = 0.068 WT + 4.281 HT - 1.730

R = 0.97 SEE = 0.216

where BMR is in MJ/24 h, weight (WT) in kg, and height (HT) in m.
SEE is the standard error of the estimate.

There was fair conformance between the standard equations of
Benedict-Levine and Schofield, which was not surprising since Schofield
incorporated Benedict's data. Karlberg's standard equation yielded
generally lower values of basal metabolism. Application of the three standard
equations to the 60 infants, ages 1 week to 1 year, described in Karlberg's
publication, resulted in the following mean values for basal metabolism:
54.6(3.2), 50.8(1.6), and 53.8(4.3) kcal/kg/d for the Benedict-Levine, Karlberg,
and Schofield equations, respectively (Figure 5). The slope relating SMR
(kcal/kg/d) and age was positive by Benedict-Levine, negative by Karlberg, and
insignificant by Schofield predictions. Differences may be explained, in part,
by the dissimilarities in subjects and experimental design, i.e., fed vs fasted
state, time of day, etc.

In our studies of energy requirements during infancy, we have
measured the basal metabolism of infants at 1 and 4 months of age. For the
purposes of this presentation, data from two publications have been compiled
(BUTTE, SMITH, and GARZA, 1989; BUTTE et al., 1989). A description of the
105 infants studied is presented in Table 3. At the time of observation,
these breast-fed (BF) and formula-fed (FF) infants were healthy and growing
adequately. Energy expenditure was measured in an indirect calorimeter for 3 to
4 consecutive hours after an ad libitum feeding of human milk or formula.
The sleeping metabolic rate (SMR) was defined operationally as the mean energy
expenditure 2 to 3 or 3 to 4 hours postprandially, whichever was smaller and/or
available. The minimal 5-minute interval observed during the SMR period was
identified and designated as minimal observable energy expenditure (MOEE).

The combined results of SMR and MOEE are shown in Table 4.
The ratio of MOEE/SMR was 0.89(0.04). SMR and MOEE were highly correlated (r =
0.97; p < 0.001). Our results did not enable us to determine whether SMR or
MOEE had reached minimum values; in our first study, energy expenditure steadily
decreased throughout the four postprandial hours. In our second study, energy
expenditure tended to plateau between the third and fourth hour of observation.

The positive linear relationship between SMR and body weight was
highly significant (Table 5A). Weight or length alone accounted for 74%
of the variability in SMR; the combination of weight and length accounted for
77% of the variability. To identify the power of body weight most suitable for
the standardization of SMR, the data were fitted to the equation:

ln(SMR) = ln(k) + In(WT)

(Table 5B; Figure 7). Using this equation, the most
suitable power was 0.9 (R2 = 0.77). Controlling for age (Table
5C), the most suitable power was 0.7. This equation accounted for 78% of the
variability in SMR. Addition of length to the model increased R2 by
1%.

Regression analysis was used to explore the predictability of SMR
by feeding mode, age, sex, weight, length, weight/length2, sum of
skinfolds, and weight gain (Table 6). The best predictive model contained
weight/length2, feeding mode, and length, and explained 78% of the
variability of SMR. Elimination of feeding mode from this model decreased
R2 to 76%. The combination of weight, length, and feeding mode also
resulted in an R2 of 78%. As expected, the anthropometric indices
were highly correlated with weight and length, which were virtually
exchangeable. Variables entered in these predictive equations were
representative of body mass and body dimension. Feeding mode was not highly
correlated with the other variables, and therefore made a small independent
contribution.

In a subset of 40 infants (BUTTE et al., 1989), estimations
of fat-free body mass (FFBM) and total daily energy expenditure (TDEE) were
available from doubly-labelled water measurements. Mean SMR was 50.4 kcal/kg/d
or 66.7 kcal/kg FFBM/d. SMR (kcal/d) was significantly correlated with FFBM (kg)
(r = 0.82) (Figure 8) and TDEE (r = 0.90) (Figure 9), while
negatively correlated with FFBM (%WT)(r = -0.69; p < 0.001). Multiple
regression analysis was used to explore the additional contribution of FFBM
derived from oxygen-18 dilution (in absolute terms and as a percentage of body
weight) to the prediction of SMR (Table 7A). The R2 from this
procedure was 0.86; the addition of FFBM did not improve the predictive ability
of the model.

Since SMR has been used to predict total daily energy expenditure,
and therefore the daily energy requirement of adults (FAO/WHO/UNU, 1985), we
explored the predictability of TDEE from SMR (Table 7B). The equation
describing SMR as a function of TDEE was:

TDEE (kcal/d) = -31 +1.4 SMR (kcal/d);R2 = 0.81,
SEE = 39.3.

The ratio of TDEE/SMR increased from 1.27(0.14) at 1 month to
1.35(0.13) at 4 months of age, as a result of the increasing mobility of the
infants. Regression analysis indicated that SMR and FFBM (absolute) were the
best predictors of TDEE (R2 = 0.84; SEE = 35.4). However, the ability
to predict the TDEE of an individual from SMR with or without FFBM is limited;
the potential error in the prediction for an individual would be approximately
±70 to 80 kcal/d.

In conclusion, SMR has been used as a proxy for the basal
metabolism of infants. SMR, under most prevailing measurement conditions,
represents energetic processes necessary for the maintenance of life, but also,
to varying extents, represents the energy cost of growth, the thermic effect of
feeding, and subtle body movement. In infancy, basal metabolism is accounted for
primarily by the brain, liver, heart, and kidney. The decline in basal
metabolism relative to body weight is secondary to the differential growth rates
of these vital organs relative to muscle and fat. The basal metabolism of
infants is roughly proportional to body weight, rather than to the fractional
power of 0.75 identified for adults. SMR (kcal/kg/d) appears to decline slightly
over the first year of life, although this finding remains controversial. Our
series of studies has shown that SMR (kcal/kg/d) is inversely related to body
weight and parameters of body fatness. SMR (kcal/kg/d) differed by feeding mode,
but not by age or sex. The parameters weight/length2, feeding mode,
and length, or weight, length, and feeding mode accounted for 78% of the
variability in SMR. In a subset analysis, FFBM did not augment the
predictability of SMR. SMR and FFBM were shown to predict 84% of the variability
of TDEE. The advances in measurements of SMR have yet to account completely for
the individual variability observed in the basal metabolism of
infants.